Description: (Taken directly from the application). The concept that (HPA) axis are functionally connected is well accepted. Cytokines are functionally connected is well accepted. Cytokines are proteins produced (ILs). These factors can enter the circulation and serve as messengers factors can enter the circulation and serve as messengers between the immune system and the HPA axis. Until now most studies of the ability conducted with the exogenous administration of single ILs. While these with the exogenous administration of single ILs. While these studies have mediating IL-induced ACTH and corticosteroid secretion, it becomes induced ACTH and corticosteroid secretion it becomes important to extend activation. We have therefore developed a model of localized tissue injury therefore developed a model of localized tissue injury induced by the peripheral inflammation increases plasma ACTH and corticosterone for 24 h. inflammation increases plasma ACTH and corticosterone for 24 h with peak endogenous corticotropin-releasing factor (CRF) significantly interferes corticotropin-releasing factor (CRF) significantly interferes with ACTH lower plasma ACTH levels, but to a lesser extent. We and others have also plasma ACTH levels but to a lesser extent. We and others have also shown inflammation is accompanied by increases in plasma IL-6 levels. Taken inflammation is accompanied by increases in plasma IL-6 levels. Taken peptides and endogenous cytokines in the stimulatory influence of peptides and endogenous cytokines in the stimulatory influence of played by these secretagogues. Under Specific Aim 1, we will measure played by these secretagogues. Under Specific Aim 1 we will measure cytokine biosynthesis in the brain. When compared to the pattern of ACTH cytokine biosynthesis in the train. When compared to the pattern of ACTH these results will allow us to determine whether ACTH/corticosterone these results will allow us to determine whether ACTH/corticosterone and/or increased synthesis within the brain. We will then use specific and/or increased synthesis within the brain. We will then use specific a physiological role in mediating activation of the HPA axis by play a physiological role in mediating activation of the HPA axis by inflammation stimulates CRF and/or VP synthesis in the brain, investigate inflammation stimulates CRF and/or VP synthesis in the brain investigate by inflammation, and test hypotheses related to the site(s) of action axis by inflammation and test hypotheses related to the site(s) of alter pathways containing these peptides. signals alter pathways containing these peptides. The experiments described in this proposal will thus provide information The experiments described in this proposal will thus provide information mediating the release of ACTH and corticosteroids caused by inflammation. mediating the release of ACTH and corticosteroids caused by inflammation. inappropriate endocrine responses to inflammatory processes. inappropriate endocrine responses to inflammatory processes.